The long-term objective of the proposed studies is to elucidate the mechanisms by which estrogens regulate the overall growth response of the uterus. The uterus responds to estrogens in a bi-phasic manner involving both early and late responses. The early responses are characterized by increases in uterine wet weight and various metabolic parameters, and the late responses are characterized by increases in uterine dry weight, protein and RNA content, and DNA synthesis. We propose to determine how the interaction of estrogen receptors with nuclear acceptor sites regulates this overall response, how different uterine responses are related, what key metabolic changes are involved in regulating estrogen stimulated uterine growth, and what other hormones affect the uterine response to estrogens. Key metabolic events that we propose to study are estrogen induced changes in RNA polymerase activities and properties, chromatin template capacity and cyclic nucleotide phosphodiesterase activity. Another major area we propose to study is the role of thyroid and pituitary hormones in regulating both the early and late uterine responses to estrogens.